I'm sure people will have discovered the papers covering the exhaustive studies on the 1-aryl-cyclohexylamine class off NMDA antagonist/DRI class (Erowid has a vault on all of that stuff) so when UK law made the scaffold illegal, the only novel alternative looked at back in the 60s was a single small study on 1-(1,2-diphenylethyl)piperidine so that was the intended lead-compound to explore the class. So, the custom-synth people weren't fantastic and they sent 1-(1,2-diphenylethyl)pyrrolidine! Idiots. Well, there is a very important relationship between the position of 1-aryl & the lone-pair of the N: (107.5 is the best as seen in Dizocilpine) so we KNEW it wouldn't have NMDA activity but wanted to confirm that it had DRI activity (NMDA antagonism without DRI activity is generally not so euphoric). Well, only a slight surprise to discover that it was subjectively identical (as far as we could tell) to prolintane. A very smooth, very selective DRI). So as soon as they DID manage to provide the specified ligand, it was immediately put through the Eunoiapharmacopia crew (hello from OranheJuice) who... ate it, because the .HCl wasn't too water soluble! Anyway, apart from discovering that isophenidine is THE one to go for (MXE nice), it's not such an interesting find... but the fact that a second benzene ring acts as a bioisostere to an N-propyl certainly WAS. So we went this way:
1-(1,2-diphenylethyl)pyrrolidine - not TOO potent, really smooth. I liked it a lot but I was told young people wanted something more so
1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone - a LOT more like pyrovalerone but had that tendency to hang on for too long. Fun for 2 hours then, like cocaine (which I don't really care for truth be told), it just hangs on. So...
1-(4-methylphenyl)-2-phenyl-2-(pyrrolidin-1-yl)ethanone - The p-Me didn't increase potency but it meant that the subjective effects tailed off much more quickly beyond the 2 hour mark and that was pyrophenidone (which I know people liked)
but we DID go further
1-(2,3-dihydro-1H-inden-5-yl)-2-phenyl-2-(pyrrolidin-1-yl)ethanone - the indene ring was added to check if it were possible to improve serotonin reuptake inhibition. Was is us or did that p-Me FEEL a bit better? If so was it S related. No.
1-(1,3-benzodioxol-5-yl)-2-phenyl-2-(pyrrolidin-1-yl)ethanone - So obviously we wanted to know if like MDPV, the MD ring would increase DRI activity. It did but it was costly and not as smooth. The p-Me was nicer.
Meanwhile we obviously tried various other N substituents (and found the QSAR was more like PCP than K). The 2-F was tasted (not by me) but the EC crew all wanted that. Turned out that the ketone->amine step via NaBH4 stripped off that -F (or indeed the -Cl) which is why 2-MeO turned up. The N-methyl & N-ethyl didn't have much activity but a series was made with various substituents at the o,m & p position (the 2-Cl 5-MeO was good, the 2-Cl-5-OH was great... but too costly).
It was interesting to know that an MD can seemingly increase VMAT-2 affinity and that it isn't strictly serotonin. I know people placed MD rings onto several rigid PEA derivatives including the phenmetrazine, phenylmethylpiperidine esters (methylphenidate/levophacetoperane) & aminorex scaffolds. It isn't rewarding. The only commonality across them all is the monosubstitution of the m or p positions. As I have posted elsewhere, a 2:1 mixture of p-Me aminorex:m-Me aminorex is like MDMA on steroids. The p is a serotonin releaser, the m is mixed but mostly a dopamine releaser. Now, existing as a zwitterion as the 4,5-dihydro-1,3-oxazol-2-amine ring does, BOTH isomers are active since the exo form overlays MDA while the endo form overlays MDA. We worked that out afterwards. All we knew was that the p alone was inactive in most people, the m alone was just a stimulant & the 1:1 was too speedy. The 2:1 has the body rushes & legs of MDA (that 'sledging' & hugging yourself stuff) AND the euphoria and entactogenic effects of MDMA.
Since those long gone days I've spotted that 5/6(M)APB is taken from a patent (that Dr. Zee guy is a liar) and wondered about related rings. I cannot recall if it was Dr. Dave or Dr. Shulgin who tried adding an -F or two onto the methylene bridge (resulting in much lower potency) but I've not come across any studies using a benzoxathiol-6-yl or related (3H-2,1-benzoxathiolyl, 1,3-dihydro-2-benzofuran, 1,3-dihydro-benzothio and so on) ring. I SUSPECT that the aromatic has to be rotatable relative to the basic amine(s) for any ring supplying a lone-pair to work and I suspect that planer (so unsaturated) increases potency and shortens at least one bond-length so there is a little more space (if the -F derivatives were less potent due to lower affinity itself due to physical size. I mean, we know PMA & PMMA are pretty dangerous and people making 'ecstacy' using them is basically guilty of intentionally poisoning people (even the 2-carbon 5HT2a ligands seem toxic) BUT I would (very cautiously) taste the benzothiophene homologues of APB. 4MTA (p-thiomethoxy) is a more potent serotonin releaser that 4MA (p-methoxy), it's the MAOI activity that seems to make it more dangerous.
Most of these I've tasted, some I've had multiple reports on, at least 2 I WISH were available (p/m aminorex & isophenidine) and there are some that look like they are worth a liik (benzothiophene) but I think if I can compress it all down to a single point. An MD ring isn't magical. You can't just add it to any stimulant with a phenyl ring and 'E it up'. I know that thiopropamine was 'rediscovered' by someone on Russian Hyperlab so I checked & the 3,4 & 5 carbon cathinone have been made and in rat models at least, 1-(5-methylthiophen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one was the most potent. I'm prepared to bet ?1 that 1-(5-methylthiophen-2-yl)-2-(pyrrolidin-1-yl)propan-1-one will prove to be mephedrone-like and MAYBE 2-(methylamino)-1-(thieno[2,3-d][1,3]dioxol-5-yl)propan-1-one & N-methyl-1-(thieno[2,3-d][1,3]dioxol-5-yl)propan-2-amine will turn out to be like inferior versions of methylone & MDMA. As we proved with the 2-carbon ketone analogues of 2CB still have 5HT2a activity. That last one was a French idea...